PTPRF is disrupted in a patient with syndromic amastia

BMC Medical Genetics

Vorasuk Shotelersuk³  Kanya Suphapeetiporn³  William A Gahl⁴  Thomas C Markello⁴  Thiti Snabboon¹  Nond Rojvachiranonda⁵  Charan Mahatumarat⁵  Verayuth Praphanphoj²  Siraprapa Tongkobpetch³  Surasawadee Ausavarat³ 

[1] Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand;Center for Medical Genetics Research, Rajanukul Institute, Bangkok, 10400, Thailand;Molecular Genetics Diagnostic Center, King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, 10330, Thailand;Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA;Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

关键词: LAR;    PTPRF;    balanced chromosome translocation;    renal agenesis;    ectodermal dysplasia;    development of breasts and nipples;    athelia;    amastia;   

Others  :  1178064
DOI  :  10.1186/1471-2350-12-46

 received in 2010-07-12, accepted in 2011-03-31,  发布年份 2011

【 摘 要 】

Background

The presence of mammary glands distinguishes mammals from other organisms. Despite significant advances in defining the signaling pathways responsible for mammary gland development in mice, our understanding of human mammary gland development remains rudimentary. Here, we identified a woman with bilateral amastia, ectodermal dysplasia and unilateral renal agenesis. She was found to have a chromosomal balanced translocation, 46,XX,t(1;20)(p34.1;q13.13). In addition to characterization of her clinical and cytogenetic features, we successfully identified the interrupted gene and studied its consequences.

Methods

Characterization of the breakpoints was performed by molecular cytogenetic techniques. The interrupted gene was further analyzed using quantitative real-time PCR and western blotting. Mutation analysis and high-density SNP array were carried out in order to find a pathogenic mutation. Allele segregations were obtained by haplotype analysis.

Results

We enabled to identify its breakpoint on chromosome 1 interrupting the protein tyrosine receptor type F gene (PTPRF). While the patient's mother and sisters also harbored the translocated chromosome, their non-translocated chromosomes 1 were different from that of the patient. Although a definite pathogenic mutation on the paternal allele could not be identified, PTPRF's RNA and protein of the patient were significantly less than those of her unaffected family members.

Conclusions

Although ptprf has been shown to involve in murine mammary gland development, no evidence has incorporated PTPRF in human organ development. We, for the first time, demonstrated the possible association of PTPRF with syndromic amastia, making it a prime candidate to investigate for its spatial and temporal roles in human breast development.

【 授权许可】

   
2011 Ausavarat et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Robinson GW: Cooperation of signalling pathways in embryonic mammary gland development. Nat Rev Genet 2007, 8(12):963-972.
• [2]Merlob P: Congenital malformations and developmental changes of the breast: a neonatological view. J Pediatr Endocrinol Metab 2003, 16(4):471-485.
• [3]Plessis G, Le Treust M, Le Merrer M: Scalp defect, absence of nipples, ear anomalies, renal hypoplasia: another case of Finlay-Marks syndrome. Clin Genet 1997, 52(4):231-234.
• [4]Picard C, Couderc S, Skojaei T, Salomon R, de Lonlay P, Le Merrer M, Munnich A, Lyonnet S, Amiel J: Scalp-ear-nipple (Finlay-Marks) syndrome: a familial case with renal involvement. Clin Genet 1999, 56(2):170-172.
• [5]Lefebvre O, Wolf C, Kedinger M, Chenard MP, Tomasetto C, Chambon P, Rio MC: The mouse one P-domain (pS2) and two P-domain (mSP) genes exhibit distinct patterns of expression. J Cell Biol 1993, 122(1):191-198.
• [6]Miscio G, Tassi V, Coco A, Soccio T, Di Paola R, Prudente S, Baratta R, Frittitta L, Ludovico O, Padovano L, et al.: The allelic variant of LAR gene promoter -127 bp T--> A is associated with reduced risk of obesity and other features related to insulin resistance. J Mol Med 2004, 82(7):459-466.
• [7]Hearn T, Renforth GL, Spalluto C, Hanley NA, Piper K, Brickwood S, White C, Connolly V, Taylor JF, Russell-Eggitt I, et al.: Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome. Nat Genet 2002, 31(1):79-83.
• [8]Podolski J, Byrski T, Zajaczek S, Druck T, Zimonjic DB, Popescu NC, Kata G, Borowka A, Gronwald J, Lubinski J, et al.: Characterization of a familial RCC-associated t(2;3)(q33;q21) chromosome translocation. J Hum Genet 2001, 46(12):685-693.
• [9]O'Grady P, Krueger NX, Streuli M, Saito H: Genomic organization of the human LAR protein tyrosine phosphatase gene and alternative splicing in the extracellular fibronectin type-III domains. J Biol Chem 1994, 269(40):25193-25199.
• [10]Schaapveld RQ, Schepens JT, Robinson GW, Attema J, Oerlemans FT, Fransen JA, Streuli M, Wieringa B, Hennighausen L, Hendriks WJ: Impaired mammary gland development and function in mice lacking LAR receptor-like tyrosine phosphatase activity. Dev Biol 1997, 188(1):134-146.
• [11]Wang Z, Shen D, Parsons DW, Bardelli A, Sager J, Szabo S, Ptak J, Silliman N, Peters BA, van der Heijden MS, et al.: Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science 2004, 304(5674):1164-1166.
• [12]Yang T, Zhang JS, Massa SM, Han X, Longo FM: Leukocyte common antigen-related tyrosine phosphatase receptor: increased expression and neuronal-type splicing in breast cancer cells and tissue. Mol Carcinog 1999, 25(2):139-149.
• [13]Eeds AM, Mortlock D, Wade-Martins R, Summar ML: Assessing the functional characteristics of synonymous and nonsynonymous mutation candidates by use of large DNA constructs. Am J Hum Genet 2007, 80(4):740-750.